Preparing the way for the understanding of a rare neurological disease

ENRAH-SME was a pioneering European Union (EU)-funded project which laid the crucial groundwork for a major breakthrough in the understanding and potential treatment of a rare childhood neurological disease.

Alternating Hemiplegia of Childhood (AHC) is a disorder that causes sporadic and unpredictable episodes of paralysis of one side of the body and then the other. Learning disabilities and other neurological symptoms are common effects of the disease. Although it typically begins prior to 18 months of age, AHC – despite its name - tends to last throughout life. A proportion of children with AHC die before reaching adulthood.

But the rarity of the disease has meant that it has often gone undiagnosed by doctors. The name AHC was only coined in 1974, and the small number of recognised and diagnosed cases since then has meant AHC has been imperfectly understood – with the inevitable result that the search for a treatment has been severely hampered.

ENRAH-SME was an EU Support Action project set up and co-ordinated by Dr Tsveta Schyns, who was prompted into action when, after her own daughter was diagnosed with AHC, she found there was a need for much greater understanding of the condition in order to help diagnose it and eventually accelerate the search for a treatment. After establishing the European Network for Research on Alternating Hemiplegia (ENRAH) in her home-city of Vienna, Dr Schyns linked up with 13 other partner groups, including research groups, patient organisations and small and medium sized enterprises (SMEs), to establish the ENRAH-SME project in 2005.

Running for a period of 27 months, the project’s key aims were to create a network of AHC expertise in Europe, bringing together paediatric neurologists, researchers and patients and patient organisations, and to improve understanding of the disease by creating a web-based registry of AHC patients across Europe, based on the identification and cataloguing of as much scientific and medical information about each case as possible. As the name of the project implied, a particular focus was to identify and harness as much relevant expertise as possible from the SME sector, including companies specialising in IT and electronic data gathering, as well as clinical research and drug development.

In the words of Dr Schyns, who happens to be a geneticist by training, although she was acting as an individual citizen and a mother in this case: “This is where you have to start if you want to know about a disease that does not even have a proper diagnosis. Setting up a clinical registry is a vital tool for further research.”

ENRAH-SME succeeded in creating a secure online database containing 157 cases of AHC, including, where available, clinical information relating to how the disease had developed at various stages in the patients’ lives – thus contributing to a far greater understanding of the disease and its diagnosis than ever before. Many relevant SMEs were recruited to the network, not only benefiting those businesses but also generating a pool of expertise and resources for other EC research programmes in thematically related areas.

Most significantly of all, the work of ENRAH-SME, and the information it gathered was an important building block for later research work, led by Duke University and the University of Utah in the US, which in 2012 identified a specific gene mutation which causes AHC in most patients. After studying the genomes of a group of 95 patients, a number that would have been impossible without the registry created by ENRAH-SME, the researchers were able to show, in a paper published in Nature Genetics, that more than 75% of patients had disease-causing mutations in one specific gene.

As Dr Schyns explains, the ENRAH-SME consortium did not itself carry out the genetic research into AHC – but it carried out the behind-the-scenes work without which that breakthrough research would never have been possible.